The purpose of this investigation is to develop an in vitro method for predicting the efficacy of topical antiviral drug therapies for oro-facial herpes simplex virus (HSV) infections. The proposed studies will test the hypothesis that an index which correlates with clinical efficacy can be derived from the ratio of the transcutaneous penetration of a drug preparation and its antiviral activity. Five antiviral drugs will be evaluated for 1) penetration of the drug through guinea pig skin in vitro in different vehicles (J)j 2) the drug concentration which produces a 50% reduction in HSV-1 plaque formation in tissue culture (MIC); and 3) the clinical response to the drug applied topically in the treatment of cutaneous HSV-1 infection in the Hubler guinea pig model. The antiviral index (J/MIC) will then be correlated with the degree of clinical response to the different antiviral formulations. If our hypothesis is valid, the antiviral index would provide a new method for assessing likely clinical efficacy of topical antiviral formulations and fill the current void between the development of structures with in vitro antiviral activity and testing of their efficacy in clinical trials of naturally occurring HSV-1 disease.